During the previous two years of effort, we have demonstrated that the Wien mass spectrometer (WMS) is capable of analyzing compounds of very high mass ((CsI)155Cs+ at 40,433d) and with very high sensitivity (1 pmol of Bovine insulin at 5,734d). The short analysis time of about 10 min/sample allows rapid optimization of instrumental operating conditions such as sample matrix composition and matrix temperature. Our primary goals will be to establish the upper mass and sensitivity capability of the LSIMS technique on the WMS and to collaborate with researchers at UCSF and elsewhere on a wide variety of problems in biochemical engineering and structural biochemistry. In support of these goals, several major improvements in the WMS are proposed: 1) Install a more powerful Wien analyzer capable of increasing mass resolution by a factor of four, without reducing sensitivity. This will increase the accuracy of mass measurement by a commensurate amount; 2) Reduce instrument background pressure by increasing pumping speed. This will improve transmission and resolution for high mass compounds; 3) Provide the instrumental capability for the analysis of negatively charged compounds; 4) Continue refinements on the ion source, probe and detector to increase sensitivity of the instrument.